Application of calcium nebulization for mass exposure to an accidental hydrofluoric acid spill.

PURPOSE: To determine the long-term prevalence and characteristics of acute hydrofluoric acid (HF) exposure in 2223 patients during the first 30 months after a mass-casualty exposure, and to confirm the antidotal effect of nebulized calcium on inhalation burns caused by HF. METHODS: This observational cohort study included patients after an HF spill in the Republic of Korea on September 27, 2012; registered patients were followed until April 2015. We assessed toxic effects, distance from spill, degree of acute poisoning, and the effect of nebulized calcium in HF-exposed individuals. RESULTS: Overall, 2223 patients received emergency management or antidote therapy for 20 days. Seventy-four of 134 patients with dermal toxicity received calcium-lidocaine gel, and 368 individuals with bronchial irritation signs received calcium gluconate via nebulizer nCG. A total 377 ampoules 786 g of calcium gluconate were used in the nCG formulation. Calcium administration did not cause adverse reactions during the observation period. Long-term cohort observation showed that 120 patients (120/2233, 5.4%) returned to medical facilities for management of HF-related symptoms within 1 month; 18 persons (18/1660, 1.1%) returned 1-3 months later with chronic cough and respiratory symptoms; and 3 patients (3/1660, 0.2%) underwent medical treatment due to upper-airway toxic symptoms more than 2 years after HF exposure. CONCLUSION: Respiratory toxicity after mass exposure to an HF spill was successfully treated by calcium nebulizer. Based on our experience, detoxification processes and the amounts of antidote stocked are important when planning for future chemical disasters at the community level.

[Effect of dinitrosyl iron complexes on erythrocyte energy metabolism under thermal trauma conditions].

The effect of dinitrosyl iron complexes (DNIC) on the energy metabolism of erythrocytes under combined thermal trauma conditions has been studied on a group of 30 Wistar rats, which was divided into 3 groups: intact (n = 10), control (n = 10), and main (n = 10). Combined thermal trauma (skin burn + thermoinhalation damage) was modeled in animals of the control and main groups. Rats of control group received infusions of sodium chloride solution (n = 10) every day. Rats of the main group obtained infusions of DNIC solution in sodium chloride. Rat blood samples were characterized by the activity of lactate dehydrogenase in direct and reverse reaction, lactate level, and coefficients of the substrate provision and energy reactions balance. It was stated, that DNIC clearly normalized the energy metabolism of erythrocytes beginning with the third day after thermal trauma onset.

Heparin/N-acetylcysteine: an adjuvant in the management of burn inhalation injury: a study of different doses.

PURPOSE: Nebulized heparin may reduce fibrin cast formation and reduce the degree of airway obstruction in burn inhalation injury. METHODS: Twenty-nine patients admitted to burn intensive care unit (ICU) within 24 hours of burn inhalation injury were included in this prospective double-blinded randomized study. Group H5 received nebulized heparin sulfate 5,000 IU, and group H10 received nebulized heparin sulfate 10,000 IU. Heparin was given in alternation with N-acetylcysteine every 2 hours. Lung injury score assessed daily for 7 days was the primary outcome. Duration of mechanical ventilation, coagulation profile, length of ICU stay, and mortality were the secondary outcomes. RESULTS: Median lung injury scores were significantly lower in group H10 on days 5 (1.9 vs 1), 6 (1.4 vs 0.5), and 7 (1.3 vs 0.5). Group H10 had also a lower duration of mechanical ventilation than did group H5 (P = .037). The groups had no significant difference in coagulation parameters, length of ICU stay (P = .17), and mortality (P = .6). CONCLUSIONS: Nebulized heparin 10,000 IU decreased lung injury scores and duration of mechanical ventilation but had no effect on length of ICU stay and mortality. Moreover, nebulized heparin 10,000 IU was safe and had no effect on coagulation parameters.

[Stepwise treatment in patients with isolated thermal inhalation injury].

AIM: To evaluate the efficiency of stepwise treatment in patients with isolated thermal inhalation injury (TIJ). SUBJECTS AND METHODS: The study enrolled 101 patients with isolated TIJ. A study group (n=56) was treated at the Pulmonology Department after managing at the Burn Center (BC); a control group (n=45) received no systematic treatment after discharging from BC. The magnitude of respiratory symptoms (according to the rating system) and external respiratory function (ERF) was evaluated and fibrobronchoscopy was made in all the included patients at their discharge from BC. On admission to the Pulmonology Department, the study group patients underwent evaluation of the magnitude of respiratory symptoms, EFR, and lung diffusing capacity, determination of blood gas composition and exercise tolerance, and chest computed tomography. Respiratory symptoms, ERF, and exercise tolerance were evaluated in all the included patients one month after hospital discharge. RESULTS: Examination at the Pulmonology Department established preserved respiratory manifestations in patients who had to continue therapy. The use of beta2-agonists or inhaled steroids used in combination or alone need, mucoregulators or antibiotics revealed the efficiency of a stepwise approach to managing patients with TIJ. CONCLUSION: There is evidence that it is expedient to perform two-stage treatment in patients with TIJ, by transferring them from BC to a specialized pulmonology hospital, which substantially enhances the efficiency of medical care for this contingent of patients.

Postexposure application of Fas receptor small-interfering RNA to suppress sulfur mustard-induced apoptosis in human airway epithelial cells: implication for a therapeutic approach.

Sulfur mustard (SM) is a vesicant chemical warfare and terrorism agent. Besides skin and eye injury, respiratory damage has been mainly responsible for morbidity and mortality after SM exposure. Previously, it was shown that suppressing the death receptor (DR) response by the dominant-negative Fas-associated death domain protein prior to SM exposure blocked apoptosis and microvesication in skin. Here, we studied whether antagonizing the Fas receptor (FasR) pathway by small-interfering RNA (siRNA) applied after SM exposure would prevent apoptosis and, thus, airway injury. Normal human bronchial/tracheal epithelial (NHBE) cells were used as an in vitro model with FasR siRNA, FasR agonistic antibody CH11, and FasR antagonistic antibody ZB4 as investigative tools. In NHBE cells, both SM (300 µM) and CH11 (100 ng/ml) induced caspase-3 activation, which was inhibited by FasR siRNA and ZB4, indicating that SM-induced apoptosis was via the Fas response. FasR siRNA inhibited SM-induced caspase-3 activation when added to NHBE cultures up to 8 hours after SM. Results using annexin V/propidium iodide-stained cells showed that both apoptosis and necrosis were involved in cell death due to SM; FasR siRNA decreased both apoptotic and necrotic cell populations. Bronchoalveolar lavage fluid (BALF) of rats exposed to SM (1 mg/kg, 50 minutes) revealed a significant (P < 0.05) increase in soluble Fas ligand and active caspase-3 in BALF cells. These findings suggest an intervention of Fas-mediated apoptosis as a postexposure therapeutic strategy with a therapeutic window for SM inhalation injury and possibly other respiratory diseases involving the Fas response.

Early single-shot intravenous steroids do not affect pulmonary complications and mortality in burned or scalded patients.

BACKGROUND AND OBJECTIVES: Inhalation injury, especially in combination with cutaneous burns, is the major cause of morbidity and mortality in patients admitted to burn care centers. Either with or without the presence of a cutaneous burn, inhalation injury contributes to high risk for developing severe pulmonary complications. Steroids may reduce a prolonged and destructive inflammatory response to toxic or allergic substances. The objective of this study was to evaluate the effect of early single-shot intravenous steroids on pulmonary complications and mortality in burned or scalded patients with or without inhalation injury. METHODS: Retrospective analysis of a prospective single center database of patients registered between 1989 and 2011 who were admitted to the intensive care unit of our burn care center after burn or scald injury. Uni-variate statistical analysis was performed comparing two groups (steroid treated vs. non steroid treated patients) with regard to clinical outcome. Main parameters were sepsis, mortality and pulmonary complications such as pneumonia, ALI and ARDS. Multi-variate analysis was used by logistic regression with mortality and pulmonary complications as the dependent variables to identify independent risk factors after burn or scald injuries. RESULTS: A total of 1637 patients with complete data were included in the present analysis. 199 (12.2%) received single-shot intravenous steroids during the prehospital phase of care. In 133 (66.8%) of these patients, inhalation injury was diagnosed via bronchoscopy. Steroid treated patients had sustained a significantly higher severity of burn than non-steroid treated patients (Abbreviated Burn Severity Index 7.1±3 vs. 6.0±2.9; p<0.001). In a multivariate analysis using a logistic regression model early intravenous steroid treatment had no significant effect on pulmonary complications and mortality. CONCLUSIONS: In our single center cohort of burned and scalded patients single-shot intravenous steroids during the pre-hospital phase of care was not associated with pulmonary complications or mortality.

Assessment of combined muscarinic antagonist and fibrinolytic therapy for inhalation injury.

This study tests the hypothesis that muscarinic receptor antagonist therapy with tiotropium bromide (tiotropium; TIO), alone or in combination with tissue plasminogen activator (TPA), can attenuate pulmonary dysfunction in sheep after smoke inhalation and burn injury. The study consisted of four study groups, sham (uninjured), control (injured and untreated), TIO (injured and treated with nebulized TIO), and TIO + TPA (injured and treated with nebulized TIO and TPA). Cardiopulmonary and ventilatory parameters were monitored for 48 hours. After killing the animal, airway obstruction, submucosal gland neutrophilia, parenchyma histopathology, and lung wet to dry weight ratios were measured. PaO2/FiO2 was significantly improved in the TIO group compared with the control group at 48 hours, 301 ± 149 vs 99 ± 33, respectively, P < .05. At 48 hours, peak airway pressures in the control, TIO, and TIO + TPA groups were 35 ± 6, 24 ± 7, and 26 ± 10, respectively, with the mean of the TIO group being significantly different from that of the control group, P < .05. A trend of decreased airway obstruction was seen in the treated animals compared with controls; however, the differences were not statistically significant. The TIO and TIO + TPA groups exhibited significant decreases in gland neutrophilia compared with the control group, P < .05. No differences in parenchyma histopathology and lung edema between injured control and treated groups were observed. Nebulization of TIO was effective in improving pulmonary performance and reducing bronchial submucosal gland neutrophilia in sheep after smoke inhalation and burn injury. There was no additive benefit to the inclusion of nebulized TPA with TIO.

Surfactant therapy for acute respiratory distress in severe pediatric burn injury: a case series.

After severe burn injury, pediatric patients often succumb to complications of respiratory failure. Surfactant has been used to improve pulmonary gas exchange for severe respiratory distress in other pediatric populations but has not been studied in pediatric burn-injured patients. Here, the authors report a case series of seven severely burned pediatric patients who received surfactant for acute respiratory distress and severe hypoxemia. Seven cases were reviewed of pediatric patients who received surfactant for severe acute respiratory distress. Data analyzed included age, TBSA burned, height, weight, mechanism of injury, total intensive care unit days, hospital days, and ventilator days. Modes of ventilation, peak inspiratory pressure, oxygen requirement, arterial blood gas analysis, blood pressure, and heart rate were analyzed before and the day following surfactant therapy. Four patients had reduced oxygen requirements following surfactant administration (FiO(2): 0.66 ± 0.23-0.48 ± 0.025). Three patients showed no reduction in oxygen requirements (FiO(2): 0.95 ± 0.09-0.90 ± 0.0). The remaining four patients who had reduced oxygen requirements received surfactant earlier following their injury (4.8 ± 0.9 days postinjury vs 17.7 ± 8 days postinjury) and had less derangement in oxygenation before surfactant dosing (PaO(2):FiO(2) ratio: 105.2 ± 26.4 vs 64.5 ± 5.2). Surfactant therapy may offer a therapeutic option during acute respiratory distress for severely burned pediatric patients. Surfactant may be useful early in the course of severe hypoxemia and acute respiratory distress but may not be effective as a salvage modality.

Use of beta-agonists in inhalation injury.

Damage to the pulmonary parenchyma from smoke represents a second cause of inhalation injury. To date, the treatment of lung injury due to smoke has been largely supportive in nature. Patients are intubated, placed on mechanical ventilation, and maintained on support until pulmonary status improves, permanent airway access obtained, or the patient dies. Given that the insult associated with inhalation injury causes direct pulmonary damage and that the lungs have the ability of absorb drugs, the use of inhaled therapies for inhalation injury is appealing. The goal of this chapter is to describe the potential role of inhalation therapies in the treatment of smoke inhalation injury.

Aerosolized anticoagulants ameliorate acute lung injury in sheep after exposure to burn and smoke inhalation.

OBJECTIVE: Acute lung injury is a detrimental complication for victims of burn accidents. Airway obstruction plays an important role in pulmonary dysfunction in these patients. In this study, we tested the hypothesis that aerosolized anticoagulants will reduce the degree of airway obstruction and improve pulmonary function in sheep with severe combined burn and smoke inhalation injury by preventing the formation of airway fibrin clots. DESIGN: Prospective, randomized, controlled, experimental animal study. SETTING: Investigational intensive care unit at a university hospital. SUBJECTS: Adult female sheep. INTERVENTIONS: After 7 days of surgical recovery, sheep were given a cutaneous burn (40% of total body surface, third degree) and insufflated with cotton smoke (48 breaths, <40 degrees C) under halothane anesthesia. After injury, sheep were placed on ventilators and resuscitated with lactated Ringer's solution. Sheep were randomly divided into five groups: sham, noninjured and nontreated (n = 6); control, injured and aerosolized with saline (n = 6); recombinant human antithrombin (rhAT) + heparin, injured and aerosolized with rhAT (290 units for each) and heparin (10,000 units for each) (n = 6); rhAT, injured and aerosolized with rhAT alone (290 units for each; n = 5); and heparin, injured and aerosolized with heparin alone (10,000 units for each; n = 5). rhAT and heparin were aerosolized every 4 hrs, starting at 2 hrs postinjury. MEASUREMENTS AND MAIN RESULTS: Cardiopulmonary hemodynamics were monitored during a 48-hr experimental time period. Control sheep developed multiple signs of acute lung injury. This pathophysiology included decreased pulmonary gas exchange and lung compliance, increased pulmonary edema, and extensive airway obstruction. These variables were stable in sham animals. The aerosolization of rhAT or heparin alone did not significantly improve deteriorated pulmonary gas exchange. However, aerosolization of these anticoagulants in combination significantly attenuated all the observed pulmonary pathophysiology. CONCLUSIONS: The results provide definitive evidence that aerosolized rhAT and heparin in combination may be a novel treatment strategy for pulmonary pathology in burn victims with smoke inhalation injury.

[Treatment of severe inhalation injury with endotracheal infusion of exogenous pulmonary surfactant].

OBJECTIVE: To explore the possibility and the effects of clinical application of exogenous pulmonary surfactant (PS). METHODS: Two burned patients with severe inhalation injury were treated with 5% emulsified porcine PS by endotracheal infusion of 10 ml every 2 hours with the assistance of mechanical ventilation. The indices of patients' oxygenation and related pulmonary dynamics were observed. RESULTS: Twenty-four hours after the application of exogenous PS, PaO(2) and PaO(2)/FiO(2) increased evidently, but (A -- a) DO(2) and RI decreased obviously and PaCO(2) sustained for the observing period. The index related pulmonary dynamics, DeltaV/DeltaP increased gradually. CONCLUSION: With the assistance of mechanical ventilation, endotracheal infusion of exogenous PS could improve oxygenation and compliance of patients with severe inhalation injury. And the patients exhibited very good tolerance to exogenous PS.

Intrabronchial surfactant application in cases of inhalation injury: first results from patients with severe burns and ARDS.

Damage to the respiratory tract caused by inhalation of toxic products of combustion with subsequent development of an acute respiratory distress syndrome (ARDS) is one of the main causes of death in burn patients. Treatment with an exogenous surfactant is a therapeutic option for which there has previously been no empirical data. We report on four severely burned patients with deep partial thickness and full thickness burns of between 40 and 70 per cent body surface area (BSA), and with inhalation injury complicated by ARDS. These patients were treated once or more than once with bovine surfactant replacement (Alveofact). In addition to biophysical and biochemical analysis, the influence of this substance on oxygenation and lung function were evaluated. After the limits of mechanical ventilation had been reached, bronchoscopic intrabronchial administration of surfactant was followed by temporarily improved gas exchange with an increase in arterial O2 partial pressure (PaO2), accompanied by a reduction in inspiratory O2 concentration (FiO2), and also improved lung compliance. All the patients survived in spite of an initially unfavourable prognosis. Replacement of exogenous surfactant in the treatment of inhalation traumatized severe burn patients with ARDS appears to show considerable promise as an approach to improving the survival chances of these high-risk patients.

Early cardiorespiratory patterns in severely burned patients with concomitant inhalation injury.

Hemodynamic and oxygenation parameters were determined during the first 24 h in 13 burned patients with concomitant inhalation injury (burn surface area 40-60 percent). In all patients right ventricular function was severely compromised evidenced as a significant increase in end-diastolic volumes, decrease in ejection fractions, low stroke work indices and increased pulmonary vascular resistances. Inotropic support with dobutamine and careful titration of volume infusion according to end-diastolic volume indices improved the hemodynamics as demonstrated by significant increases in right ventricular ejection fractions in all patients without any changes in mean arterial pressures, urine output and oxygenation. Assessment of ventricular performance by a specially designed pulmonary artery catheter is helpful in the management of severely burned patients with concomitant inhalation injury.

[Aspiration of petroleum by a "fire-eater"]. / Die Aspiration von Petroleum be einem "Feuerpsucker".

A 21-year-old man suffered from cough, dyspnoea and hemoptysis following accidental aspiration of petroleum. Chest x-ray and computerized tomography one day after the aspiration showed infiltrates in the lower fields. Fiberbronchoscopy revealed severe bronchitis without any signs of necrosis. Flunisolide inhalation (200 micrograms/d) and intravenous application of prednisolone (50 mg/d) and clindamycine (600 mg/d) improved pulmonary function within a few days. The infiltrates resolved over the following two weeks. This favourable result clearly shows that conservative treatment has a role in petroleum aspiration.

[An experimental observation of effect of tetrandrine on pulmonary dysfunction in rabbit model of smoke inhalation injury].

A rabbit model with severe smoke inhalation injury was adopted to observe the effect of tetrandrine, a calcium antagonist, on pulmonary dysfunction after smoke inhalation during 24 hours post injury. It was found that tetrandrine could decrease the permeability of pulmonary and tracheal vascular permeability (p < 0.01), reduce lung edema and improve the function of respiration. These results imply that tetrandrine might be used in the treatment of inhalation injury.